Even today, about 30 years after its development, amphotericin B is widely used as an important antifungal agent which may be administered to the entire body and which exhibits reliable effects. However, this substance causes serious side effects such as hemolytic toxicity and nephrotoxicity etc.
In recent years, the above-mentioned disadvantages of amphotericin B are being eliminated by its use as a liposomal preparation comprising a phospholipid, etc. or as a fatty emulsion prepared by emulsifying a simple lipid with a phospholipid.
It has been known that amphotericin B does not readily dissolve in such lipids. In the past, therefore, two methods have existed for the production of these preparations, which are (1) a method wherein amphotericin B and a lipid are added to a solvent such as chloroform, methanol, dimethylsulfoxide, etc., the solvent is removed after uniform solution, water is added thereto for emulsification, and (2) a method wherein amphotericin B is dissolved together with sodium deoxycholate in a solvent such as dimethylacetoamide, etc., and the solution is then added to a fatty emulsion. The disadvantages here are that in method (1), it is not possible to eradicate the possibility of the harmful solvent being left and in method (2), in addition to the same disadvantage of method (1), the irritative and hemolytic synthetic surfactant sodium deoxycholate, must necessarily be included in the preparation, and the amphotericin B is not completely encapsulated in the particles of the fatty emulsion.
In Japanese Patent Application Disclosure HEI 1-160915, a technique is disclosed for drying a liposomal preparation of amphotericin B after forming a composite of protonized distearoylphosphatidyl glycerol and amphotericin B beforehand in a mixture of chloroform and methanol, however, this requires the use of a harmful solvent during production, and residues thereof have caused major problems.
In light of these circumstances, the object of the present invention has been, from its inception, to obtain a stable, homogeneous fatty emulsion containing amphotericin B without the use of harmful substances during the production thereof.